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Publication
Dual Modulation of Prostaglandin E2 Receptors EP3 and EP4 Protects ß-Cell Mass
in a Model of Aggressive Autoimmune Inflammation.
Authors Burkett JB, Fuhr J, Falk AC, Dadi P, Del Bene AN, Lucerne A, McNitt D, Clark LM,
Maxwell M, Gaeth V, Allen K, Jacobson D, Moore DJ, Wilson CS, Gannon M
Submitted By Submitted Externally on 8/19/2026
Status Published
Journal Diabetes
Year 2026
Date Published 7/31/2026
Volume : Pages Not Specified : Not Specified
PubMed Reference 42536447
Abstract Modulation of prostaglandin E2 (PGE2) signaling improves ß-cell health and
survival. In this study, we examined whether these ß-cell effects could be
harnessed alongside known PGE2-mediated immunomodulation to ameliorate ß-cell
loss in a model of severe islet autoimmunity. Simultaneous pharmacological
blockade of the EP3 receptor and activation of the EP4 receptor maintain mature
ß-cell mass, ameliorate the proinflammatory insulitic microenvironment, and
alter ß-cell stress responses in female nonobese diabetic mice undergoing
aggressive inflammatory assault. EP modulation shows promise to support ß-cell
resiliency and reduce inflammation in a setting of autoimmune attack, such as
type 1 diabetes.




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